Asymmetric catalysis using a chiral supramolecular box

18 04 2012

Self-Assembly of a Confined Rhodium Catalyst for Asymmetric Hydroformylation of Unfunctionalized Internal Alkenes

Tendai Gadzikwa, Rosalba Bellini, Henk L. Dekker & Joost N. H. Reek*

J. Am. Chem. Soc., 2012, 134 (6), 2860; DOI: 10.1021/ja211455j

A synopsis by Yazmary Melendez

In this article, J. Reek et al. continue their work developing encapsulated catalysts for the selective hydroformylation of unfunctionalized internal alkenes. They created a supramolecular box using 3 ([ZnII(salphen)]) as the template and 2 (a chiral phosphonyl-based ligand) as the dipyridyl pillars. The choice for 2 was made because, once the box self-assembled, the conformation would bring two phosphorus atoms in close proximity. Once the active catalyst was formed, the cavity within the box would be sterically crowded enough to diminish the conformational freedom of the alkenes and thus enhance the stereoselectivity.

They confirmed the assembly with proton NMR and confirmed it was a discrete structure via a titration, which was monitored by circular dichroism. They also used a diffusion NMR experiment to determine the amount of each compound in the structure and concluded the results were consistent with that of a 2+2 structure, which was also consistent with the computational models.

After obtaining the desired supramolecule, they tested its use in Rh-catalyzed asymmetric hydroformylation of cis- and trans-2-octene. They used two monodentate ligands (1 and 2) to compare this function in both, and observed in both cases a preference for aldehyde a. Although, when 2 was used in box 1, they observed the regioselectivity had reversed, causing a mild shift in favor of aldehyde b.  They also observed that the use of ligand 1 in the reaction increased the ratio of the R enantiomer of aldehyde b from 61 to 86%. Afterwards, they tested the substrate scope for 1 by doing hydroformylation reactions on a series of cis- and trans-2-alkenes. Using ligand 1, they observed the systems favored the formation of the innermost aldehyde with the trans-2-olefins yielding 80% of the major enantiomer the cis- isomers yielded 90%.

They performed further experiments to test out the overall performance as well as the stability of the ligand. In order to do this, they studied its performance at high temperature, undergoing the catalysis at 70 °C. The results suggested that the system still exhibited high enantiomeric ratios for the innermost aldehyde while similar experiments with ligand 2 produced primarily racemic mixtures.

After reading this paper, I thought it was well constructed in the sense that all the experiments I assumed they needed to do were reported. They confirmed the type of assembly and underwent a lot of studies to confirm their original assumptions regarding the enhanced selectivity afforded by the smaller the box’s cavity. I can’t really criticize their experimental design or their results. I think, however, the figures were lacking a little bit. Specifically, since they were all grayscale, when you take a look at Figure 1, for example, you can’t really appreciate the Spartan PM3 structure of the supramolecule. Furthermore, I think that the numbering was somewhat confusing, since they used numerals to identify everything. I think it would’ve been nicer if they used 1, 2 and 3 for the supramolecules, the template and the pillars (respectively), like in the paper, and then when they were to talk about the ligands and such they could’ve used roman numbers or Greek letters or something else. That way, when they talk about 1, for example, it would’ve been unambiguous that they were referring to the supramolecule and not the first ligand. I just found this issue confusing when I read it the first time.




11 responses

19 04 2012
Luis Negrón

In this article we can see a very efficient application using a combination of supramolecular and inorganic chemistry to do organic reactions. In the reported work of Reek and co workers, you will find the design of a “supramolecular box” to function as a rhodium catalyst for asymmetric hydroformylation of internal alkenes. Like some of his previous work, Reek use Zn (salphen) complexes as building blocks, but this time to react or functionalize with 3-PyMonoPhos and then Rh complex to form the supramolecular catalyst. After they confirm a “discrete” assembly of the supramolecular box, they studied the catalytic activity of hydroformylation of internal alkenes. In contrast of obtaining aldehyde “a” by using the pyridylphosphine, the obtain aldehyde “b” by using this supramolecular catalyst.

The part that I was focusing in the paper or that was interesting for me was the fact of having a supramolecular catalyst and what kind of advantages this have in comparison with other reported or conventional catalysts. In fact, there is not a universal catalyst to every reaction. For that reason, the catalyst has to adjust to a specific reaction. If the catalyst doesn’t work for a specific reaction or a given temperature, it gets discarded or found another application. However, for a supramolecular catalyst, you can modify your catalyst without the limitation of covalent bonds, having a strong tool for design in catalysis.

In this case, coordination chemistry is incorporated in this “supramolecule” but this “self-assembly” doesn’t looks like a reversible process. Also, It’s interesting to see how “robust” is this system according with the mentioned presence of ligand free rhodium. There are many factors that makes the development of these systems attractive like if they will expand the library of catalyzed molecules (other functional groups) or they will expand the library of catalysts (using building blocks like Zn(porphyrin)). It will be interesting the behavior of these supramolecular catalysts by this approach against functionalized internal alkenes.

About Yazmary Synopsis, this is an article with a proper short length, because is a continuation of Reek’s work and for that reason I founded the synopsis well correlated with the article story. The main findings in terms of background, supramolecular characterization and catalytic role were discussed very well. Yazmary criticize very well the article’s organization but I was expecting some analysis about the use of supramolecular catalysts in this area. The picture is simple but with good information, it will help a lot for the article’s main idea.

19 04 2012
Maxier A. S.

Reek et al. presets a modification of previous work of a regioselective and enantioselective supramolecular catalyst for the hydroformylation of alkenes. This catalyst was formed by the [ZnII(salphen)] (3) as the box and a chiral phosphonyl ligand as the dipyridyl pillars (1,2). By 1H-NMR and diffusion NMR they confirmed their assembly corresponding to a 2+2 assembly, as they designed with a computational model. They tested the catalyst using Rh asymmetric hydroformof cis and trans-2-ctene. They showed selectifity for the aldehyde a but when 2 was used in the box of one the product was mainly aldehyde b. When the temperature was raised the selectivity of both cases decreased but 1 maintained mayor selectivity than 2,

I believe that the paper in general was interesting. They are developing a ver complex system to improve selectivity in what they teach in undergrad studies as a “generic”, via other methods of course. From what I understood they used a model to predict what symmetry they could expect, we use it to confirm our experimental symmetries, so I’m not clear on the rational behind that. Other than that, they showed a series of experiments to study the characterization and selectivity of each catalyst that I believe provides the appropriate data. Narrative, they do give a reasonable discussion of results, but it seemed like they were trying to bulk up as much data they could in the short space that they had.

About Yaz’s synopsis, I think she did a good job segmenting the experiments by its purposes and the cartoon helped visualize the box way better. Looking forward for this discussion.

19 04 2012

Reek and colleagues report the regioselective and enantioselective supramolecular catalyst for the synthesis of hydroformylation of alkenes. This represents a very useful application that combined supramolecular, inorganic and organic chemistry. The reported supramolecular box function as a rhodium catalytic with a restricted chiral pocket that minimize the conformational freedom. They confirmed the formation of a 2+2 complex by NMR, circular dichroisum and diffusion NMR experiment. To test their system they us it for the asymmetric hydroformylation of cis and trans-2-octene.

This article has the proper length since it is a continuation of a previous work. Although I find the figures I little bit plain, specially the structural model in which the chiral pocket is really difficult to see. About Yaz synopsis, I founded to be very well written and summarized. The picture is simple but it has all the right information, but for the next time it needs to be sexy.

19 04 2012

This article by the Reek Group describes the synthesis of a supramolecular catalyst for the enantioselective hydroformilation of internal alkenes. Since the alkenes are not functionalized it is very difficult for a catalyst to achieve selectivity. This is because the catalyst cannot differentiate between the sides of the alkene because both sidechains have similar properties, being different only in length. By enclosing the catalyst in a supramolecular box, steric effects gave the catalyst enantio selectivity. In general, the catalyst favored the formation of the R-b product. The importance of these results is highlighted by the fact that commercially available catalysts pale in comparison to the supramolecular version. They need to improve their conversion rate though, it was around 10-20%.

I really like this article. We are used to reading articles in which supramolecules are being characterized or discovered. This article focused on actually making a supramolecule and then having it perform a certain function which in this case is catalyzing a reaction. After reading the article, Yazmary’s synopsis seems on point. I can’t really criticize the spelling or grammar of the synopsis. I have to agree on the comment of the Spartan model. It really is not that good even after opening the image in my browser. However, this is a really minor thing and probably not even worth pointing out.

19 04 2012
Diana S.

This week we have Reek et al. presenting the formation of an artificial “enzyme”: a self- assembled capsule which binds an active site anchored inside. I really liked the idea, mimicking a mechanism so well exploited by nature, and was rather surprised that this wasn’t stressed out more by the authors. Perhaps its already been invoked in too many papers to make it an interesting case out of it, but I haven’t read any. Anyway, the efficiency achieved by nature is hard to compete against.
The mayor strength of the paper was drawn from the excellent regio-/enantio- meric selectivites of the capsule, comparable to the best in the market. This part was sadly, in my opinion, quite confusingly explained in the text. I’ll admit it’s not an easy task to take into account %conversion, er, and rr at the same time, but perhaps relying more on the figures could’ve helped. Which brings me to one of the points commented by the blogger: figures are a strong tool that can contribute greatly to the readability of the paper, and they might have used them better. I personally would recommend a cartoon/3D depiction of the capsule and/or active site that the authors are proposing to help show the design of their catalyst, which they can back up very well with their data.
The synopsis was overall, ok. Paragraph 3 was even more confusing than the paper. The critics to the paper where good, and I agree with the blogger that the authors really should consider that JACS doesn’t charge for colors in their figures (maybe they tried Angew Chemie before JACS! ☺). The blog picture is quite simple (artistically), but eloquent.

19 04 2012
Ana Victoria

The Reek group has previously reported an encapsulated catalyst for the selective hydroformylation of unfunctionalized internal alkenes. The catalyst presented the ability to distinguish between the C3 and C2 carbons of the 2-octene. Therefore, it was anticipated that the encapsulation would improve selectivity for the asymmetric variant of the reaction also. To do this, they needed to assemble a ligand that would bind the metal center minimizing conformational freedom. A self-assembled bidentate ligand that anchors a Rh catalytic center was created to achieve this. NMR experiments and circular dichroism confirmed the product. The confinement effects in the hydroformylation of unfunctionalized internal alkenes was proven on the asymmetric reaction. The article focused on describing the supramolecule and the enantioselectivity. This is relevant because of the function of the supramolecle in catalyzing a reaction. The synopsis is good, it had the appropriate flow of the article and I agree with her opinion on the figures.

19 04 2012
Rocio Roque

Reek and coworkers present the synthesis of a supramolecular catalyst for the regioselective and enantioselective hydroformilation of alkenes. A supramolecular box was created using 3 ([ZnII(salphen)]) and a chiral phosphonyl ligand as the dipyridyl pillars (1,2). They used diffusion NMR and 1H-NMR to confirm the formation of a 2+2 assembly. Later, they tested the catalyst by doing hydroformylation reactions on a series of cis- and trans-2-alkenes.

I really enjoyed the reading of the paper. The narrative seemed ok and the main findings were well discussed. Yazmary’s synopsis was well written. Her picture was simple but conveyed the main message. Although I do agree with her criticism on the last part, I think she gave it to much importance…Anyhow, I’m looking forward to her discussion on tomorrow’s GM.

20 04 2012

In this article J. N. H. Reek et al illustrated the asymmetric hydrformylation of unactivated (unfunctionalized) olefins with regio and remarkable enantioselectivity.
The authors have prepared a supramolecular “box” and explained the uses of ligand 3-pyridyl-substituted monodentate phosphoramidite ligands (2) as pillars of such a “box” that can bring two phosphorus atoms into close proximity, affording a selfassembled chiral bidentate ligand (1). The generation of bis-ligated Rh(I) decreases the conformational freedom around the active site and that leads to good selectivity.
Interestingly, they used circular dichroisum and diffusion NMR experiments to confirm the formation of a 2+2 complex, but I don’t have any idea about this, if Yaz explains it, I would be happy.
This is very good article for any chemists but still it needs to improve in enantioselectivity and also regioselectivity. About the synopsis, it is good and also the figures illustrating the concept of journal in simplicity.

20 04 2012

In this paper, Reek and his coworkers present their work in the development of a regio- and enantioselective metal catalyst that is encapsulated by self-assembled supramolecular “boxes”. They constructed these boxes by using bis-[ZnII(salphen)] (2) and a chiral phosphorous-based ligand (3). The performed several studies (1H-NMR, diffusion NMR and CD) that confirm that their box (structure 1) was a discrete structure composed of a 1:1 ratio of 2 and 3. These studies also confirmed that the boxes showed mostly a 2+2 assembly of 2 and 3, which was in accordance with their computational models.
After they finished building their box, they decided to compare two different ligands, a monodentate (2) and a bidentate (1) ligand, in a Rh catalyzed asymmetric hydroformilation reaction. They observed that in the absence of structure 1, ligand 2 produced mostly aldehyde b, but when structure 1 was incorporates, the reverse results were observed. They also specify that ligand 1 outperforms two commercially available bidentate ligands. I agree with them in the fact that ligand 1 does seem to have more selectivity, but it doesn’t always have a good % conversion, so I’m not sure how to compare these two factors.
They also did several more studies with ligand 1 and different 2 cis and trans-2-alkenes. Overall they found out that the their ligand showed a general selectivity to produce the inner most aldehyde.
I have to say, I think the paper was well written. The narrative was well done, they presented a good analysis of their results and I think that they performed enough experiments to support their work. However. I agree with Yazmary in the fact that they could have done better in numbering their compounds. Using the same numbers for everything was really confusing. Also the pictures were not very helpful (again I agree with Yaz). About her synopsis, I found it a little bit confusing sometimes, but overall it was really helpful. She describe the main aspects of the paper and gave a good constructional criticism. The picture is nice, and describes the main idea of the paper.

20 04 2012

Among all the current challenges in organic synthesis Reek and colleagues reported on the enantioselective hydroformylation of unfunctionalized internal alkenes by means of substrate confinement within a supramolecular “box” as a tool to enhanced product selectivity. Reek’s have some history in the development of Rh-based catalysts for hydroformylations of unmodified alkenes. However when compare to conventional catalyst for hydroformylation, this article focus on the structure confinement towards product selectivity. The further application of his work seems feasible considering the relatively simple way of preparing the actual supramolecular “box” and active catalyst however the challenges behind the synthesis of the “pieces” of the “box” might be a drawback. In general the authors evaluated their system against a small library of unmodified alkenes varying in their length and cis/trans conformation. The authors contrast the results for their catalyst against commercially available catalyst however within their library of substrates the more “linear” examples are only compared only against styrene which is vinyl benzene. Therefore, they should have also included at least allylbenzene or but-3-enylbenzene to make a more appropriate assessment of the limitations of their “box”.
In general the flowing of the narrative is interrupted by the different names/words used to describe their system like when they use the word ligand X instead of compound X which is simpler. It is confusing since for example I associate the word ligand with the parts of the box directly interacting with the Rh atom. As Yazmary mentioned this article lacks a good figure with a model of the system having a substrate inside its cavity since the only two images included in the manuscript/SI are not appropriate to visualize this. Yazmary’s synopsis include a critical evaluation of the article and summarize the main findings in an engaging way but I suggest her that in the future when evaluating an article that compares a library of compounds is good to question whether that library lacks essential/representative examples. Her picture highlights the main strategy of the authors in a simplistic yet effective representation. I recommend her that when having a white background is more appropriate to use colors darker than the violet/pink color of the alkene. Another strategy to improve the figure is to increase the line with of the kekulé structures.

20 04 2012

In this blog post Yaz is summarizing a synthetic methodology communication where Rhodium is used to catalyze a hydroformilation of internal alkenes. In essence assymetric catalysis are guided by and assembly process where a specific conformation of the substrate recognize an auxiliary molecule in a self-assembly fashion. Usually synthetic chemist describes the process from a perspective very different to that use by supramolecular chemist. Here, in contrast, Reek and coworkers used an elegant way to report and explain the findings of this methodology taking advantage of the fact that the catalytic molecule is made through self-assembly and that the substrate/catalytic complex is a supramolecule.
The article had a good narrative and was easy to fallow but I think they didn’t use the figure space in an efficient way. Figure 1 is confusing; in my opinion a balanced chemical reaction should have all reagents in it. In this case it’s difficult to decipher what is the molecular composition of 1-CORhH-octene. I didn’t like the figure.
The blog post was clear but I think it gives too much information making the synopsis too long for this short paper. The cartoon was good, the authors should follow Yaz example in making clear and comprehensible drawings.

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